Amphiphilic entity nanoparticles

Abstract

The present invention provides nanoparticle compositions comprising AE nanoparticles. The present invention provides AE nanoparticles comprising one or more amphiphilic entities and pharmaceutical compositions comprising AE nanoparticles. The present invention provides methods of manufacturing AE nanoparticles. The present invention provides methods of delivering a biologically active agent to a subject by administering AE nanoparticles containing a biologically active agent to a subject.

1 . A nanoparticle composition comprising a population of particles, wherein the majority of particles have diameters between approximately 10 and approximately 300 nanometers, and wherein the particles comprise one or more amphiphilic entities. 
     
     
         2 . The nanoparticle composition of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 250 nanometers. 
     
     
         3 . The nanoparticle composition of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 200 nanometers. 
     
     
         4 . The nanoparticle composition of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 150 nanometers. 
     
     
         5 . The nanoparticle composition of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 120 nanometers. 
     
     
         6 . The nanoparticle composition of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 100 nanometers. 
     
     
         7 . The nanoparticle composition of  claim 1 , wherein the majority of particles have a range of diameters between approximately 10 and approximately 50 nanometers. 
     
     
         8 . The nanoparticle composition of  claim 1 , wherein the population of particles is substantially free of particles having a diameter in excess of 300 nm. 
     
     
         9 . The nanoparticle composition of  claim 1 , wherein fewer than 50% of the particles have a diameter in excess of 300 nm. 
     
     
         10 . The nanoparticle composition of  claim 1 , wherein fewer than 25% of the particles have a diameter in excess of 300 nm. 
     
     
         11 . The nanoparticle composition of  claim 1 , wherein fewer than 10% of the particles have a diameter in excess of 300 nm. 
     
     
         12 . The nanoparticle composition of  claim 1 , wherein fewer than 5% of the particles have a diameter in excess of 300 nm. 
     
     
         13 . The nanoparticle composition of  claim 1 , wherein fewer than 1% of the particles have a diameter in excess of 300 nm. 
     
     
         14 . The nanoparticle composition of  claim 1 , wherein the population of particles is substantially free of particles having a diameter in excess of 200 nm. 
     
     
         15 . The nanoparticle composition of  claim 1 , wherein fewer than 50% of the particles have a diameter in excess of 200 nm. 
     
     
         16 . The nanoparticle composition of  claim 1 , wherein fewer than 25% of the particles have a diameter in excess of 200 nm. 
     
     
         17 . The nanoparticle composition of  claim 1 , wherein fewer than 10% of the particles have a diameter in excess of 200 nm. 
     
     
         18 . The nanoparticle composition of  claim 1 , wherein fewer than 5% of the particles have a diameter in excess of 200 nm. 
     
     
         19 . The nanoparticle composition of  claim 1 , wherein fewer than 1% of the particles have a diameter in excess of 200 nm. 
     
     
         20 . The nanoparticle composition of  claim 1 , wherein the population of particles is substantially free of particles having a diameter in excess of 120 nm. 
     
     
         21 . The nanoparticle composition of  claim 1 , wherein fewer than 50% of the particles have a diameter in excess of 120 nm. 
     
     
         22 . The nanoparticle composition of  claim 1 , wherein fewer than 25% of the particles have a diameter in excess of 120 nm. 
     
     
         23 . The nanoparticle composition of  claim 1 , wherein fewer than 10% of the particles have a diameter in excess of 120 nm. 
     
     
         24 . The nanoparticle composition of  claim 1 , wherein fewer than 5% of the particles have a diameter in excess of 120 nm. 
     
     
         25 . The nanoparticle composition of  claim 1 , wherein fewer than 1% of the particles have a diameter in excess of 120 nm. 
     
     
         26 . The nanoparticle composition of  claim 1 , wherein the difference between the minimum particle diameter and the maximum particle diameter does not exceed approximately 600 nm. 
     
     
         27 . The nanoparticle composition of  claim 1 , wherein the difference between the minimum particle diameter and the maximum particle diameter does not exceed approximately 500 nm. 
     
     
         28 . The nanoparticle composition of  claim 1 , wherein the difference between the minimum particle diameter and the maximum particle diameter does not exceed approximately 400 nm. 
     
     
         29 . The nanoparticle composition of  claim 1 , wherein the difference between the minimum particle diameter and the maximum particle diameter does not exceed approximately 300 nm. 
     
     
         30 . The nanoparticle composition of  claim 1 , wherein the difference between the minimum particle diameter and the maximum particle diameter does not exceed approximately 200 nm. 
     
     
         31 . The nanoparticle composition of  claim 1 , wherein the difference between the minimum particle diameter and the maximum particle diameter does not exceed approximately 100 nm. 
     
     
         32 . The nanoparticle composition of  claim 1 , wherein the difference between the minimum particle diameter and the maximum particle diameter does not exceed approximately 50 nm. 
     
     
         33 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter of 300 nm. 
     
     
         34 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter of 200 nm. 
     
     
         35 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter of 150 nm. 
     
     
         36 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter of 100 nm 
     
     
         37 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter of 75 nm. 
     
     
         38 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter of 50 nm. 
     
     
         39 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter ranging between 100-300 nm. 
     
     
         40 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter ranging between 50-250 nm. 
     
     
         41 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter ranging between 60-200 nm. 
     
     
         42 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter ranging between 65-150 nm. 
     
     
         43 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter ranging between 70-130 nm. 
     
     
         44 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter ranging between 80-110 nm. 
     
     
         45 . The nanoparticle composition of  claim 1 , wherein the particles have an average diameter ranging between 90-100 nm. 
     
     
         46 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition is substantially free of toxic solvents. 
     
     
         47 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises less than 50% of toxic solvents. 
     
     
         48 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises less than 25% of toxic solvents. 
     
     
         49 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises less than 10% of toxic solvents. 
     
     
         50 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises less than 5% of toxic solvents. 
     
     
         51 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises less than 1% of toxic solvents. 
     
     
         52 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition is stable. 
     
     
         53 . The nanoparticle composition of  claim 1 , wherein the majority of particles are stable for at least 1 day. 
     
     
         54 . The nanoparticle composition of  claim 1 , wherein the majority of particles are stable for at least 2 weeks. 
     
     
         55 . The nanoparticle composition of  claim 1 , wherein the majority of particles are stable for at least 2 months. 
     
     
         56 . The nanoparticle composition of  claim 1 , wherein the majority of particles are stable for at least 5 months. 
     
     
         57 . The nanoparticle composition of  claim 1 , wherein the majority of particles are stable for at least 12 months. 
     
     
         58 . The nanoparticle composition of  claim 1 , wherein the majority of particles are stable for at least 24 months. 
     
     
         59 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to high shear force. 
     
     
         60 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to high shear force for less than 10 minutes. 
     
     
         61 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to high shear force for less than 2 minutes. 
     
     
         62 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to high shear force for less than 1 minute. 
     
     
         63 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to high shear force for less than 30 seconds. 
     
     
         64 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to pressures greater than 3,000 psi. 
     
     
         65 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to pressures greater than 10,000 psi. 
     
     
         66 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to pressures greater than 18,000 psi. 
     
     
         67 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by exposure to pressures greater than 24,000 psi. 
     
     
         68 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by microfluidization. 
     
     
         69 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by microfluidization at a pressure greater than 3,000 psi. 
     
     
         70 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by microfluidization at a pressure greater than 10,000 psi. 
     
     
         71 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by microfluidization at a pressure greater than 18,000 psi. 
     
     
         72 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by microfluidization at a pressure greater than 24,000 psi. 
     
     
         73 . The nanoparticle composition of any one of  claims 7 i- 7 m, wherein the microfluidization is single-pass microfluidization. 
     
     
         74 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by cavitation. 
     
     
         75 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition was generated by high pressure homogenization. 
     
     
         76 . The nanoparticle composition, wherein the amphiphilic entity is generally described. 
     
     
         77 . The nanoparticle composition, wherein the amphiphilic entity is specifically described. 
     
     
         78 . The nanoparticle composition of  claim 1 , wherein the composition comprises one or more biologically active agents. 
     
     
         79 . The nanoparticle composition of  claim 78 , wherein the biologically active agent is encapsulated within the particles. 
     
     
         80 . The nanoparticle composition of  claim 78 , wherein the biologically active agent is nestled within the micellar membrane. 
     
     
         81 . The nanoparticle composition of  claim 78 , wherein the biologically active agent is associated with the particle surface. 
     
     
         82 . The nanoparticle composition of  claim 78 , wherein the biologically active agent is one or more botulinum toxins. 
     
     
         83 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is selected from the group comprising type A, type B, type C 1 , type C 2 , type D, type F, and type G. 
     
     
         84 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is type A botulinum toxin. 
     
     
         85 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is a botulinum toxin complex. 
     
     
         86 . The nanoparticle composition of  claim 85 , wherein the botulinum toxin complex comprises a non-toxin hemagglutinin protein and a non-toxic non-hemagglutinin protein. 
     
     
         87 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is incorporated within an albumin matrix. 
     
     
         88 . The nanoparticle composition of  claim 87 , wherein the albumin is human albumin. 
     
     
         89 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is a purified botulinum toxin protein or fragment thereof. 
     
     
         90 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is isolated, or substantially isolated, from other proteins. 
     
     
         91 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is isolated, or substantially isolated, from non-toxin proteins. 
     
     
         92 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is isolated from  Clostridium botulinum.    
     
     
         93 . The nanoparticle composition of  claim 82 , wherein the botulinum toxin is chemically synthesized. 
     
     
         94 . The nanoparticle composition of  claim 82  wherein the botulinum toxin is produced recombinantly. 
     
     
         95 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition can penetrate skin without altering or changing the skin. 
     
     
         96 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition can penetrate skin without the use of skin permeation enhancers or abrasives. 
     
     
         97 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition can penetrate the top layer of skin without the use of skin permeation enhancers or abrasives. 
     
     
         98 . The nanoparticle composition of  claim 97 , wherein the top layer of the skin is the surface of the stratum corneum. 
     
     
         99 . The nanoparticle composition of  claim 97 , wherein the top layer of the skin includes dermal pores. 
     
     
         100 . The nanoparticle composition of  claim 97 , wherein the top layer of the skin includes dermal glands. 
     
     
         101 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition can penetrate skin without the use of chemical permeation enhancers or abrasives. 
     
     
         102 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition can penetrate skin without the use of mechanical permeation enhancers or abrasives. 
     
     
         103 . The nanoparticle composition of  claim 1 , wherein the particles can penetrate skin without altering or changing the skin. 
     
     
         104 . The nanoparticle composition of  claim 1 , wherein the particles can penetrate skin without the use of skin permeation enhancers or abrasives. 
     
     
         105 . The nanoparticle composition of  claim 1 , wherein the botulinum toxin can penetrate skin without altering or changing the skin. 
     
     
         106 . The nanoparticle composition of  claim 1 , wherein the botulinum toxin can penetrate skin without the use of skin permeation enhancers or abrasives. 
     
     
         107 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises an oil. 
     
     
         108 . The nanoparticle composition of  claim 107 , wherein the oil is selected from the group consisting of almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, chamomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macadamia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils, and combinations thereof. 
     
     
         109 . The nanoparticle composition of  claim 107 , wherein the oil is soybean oil. 
     
     
         110 . The nanoparticle composition of  claim 107 , wherein the oil is selected from the group consisting of butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, Labrafac WL 1349, and combinations thereof. 
     
     
         111 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition does not have more than one oil. 
     
     
         112 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises a surfactant. 
     
     
         113 . The nanoparticle composition of  claim 112 , wherein the surfactant is a nonionic detergent. 
     
     
         114 . The nanoparticle composition of  claim 112 , wherein the surfactant is selected from the group consisting of phosphoglycerides; phosphatidylcholines; dipalmitoyl phosphatidylcholine (DPPC); dioleylphosphatidyl ethanolamine (DOPE); dioleyloxypropyltriethylammonium (DOTMA); dioleoylphosphatidylcholine; cholesterol; cholesterol ester; diacylglycerol; diacylglycerolsuccinate; diphosphatidyl glycerol (DPPG); hexanedecanol; fatty alcohols such as polyethylene glycol (PEG); polyoxyethylene-9-lauryl ether; a surface active fatty acid, such as palmitic acid or oleic acid; fatty acids; fatty acid monoglycerides; fatty acid diglycerides; fatty acid amides; sorbitan trioleate (Span 85) glycocholate; sorbitan monolaurate (Span 20); polysorbate 20 (Tween-20); polysorbate 60 (Tween-60); polysorbate 65 (Tween-65); polysorbate 80 (Tween-80); polysorbate 85 (Tween-85); polyoxyethylene monostearate; surfactin; a poloxomer; a sorbitan fatty acid ester such as sorbitan trioleate; lecithin; lysolecithin; phosphatidylserine; phosphatidylinositol; sphingomyelin; phosphatidylethanolamine (cephalin); cardiolipin; phosphatidic acid; cerebrosides; dicetylphosphate; dipalmitoylphosphatidylglycerol; stearylamine; dodecylamine; hexadecyl-amine; acetyl palmitate; glycerol ricinoleate; hexadecyl sterate; isopropyl myristate; tyloxapol; poly(ethylene glycol)5000-phosphatidylethanolamine; poly(ethylene glycol)400-monostearate; phospholipids; synthetic and/or natural detergents having high surfactant properties; deoxycholates; cyclodextrins; chaotropic salts; ion pairing agents; and combinations thereof. 
     
     
         115 . The nanoparticle composition of  claim 112 , wherein the surfactant is Tween 80. 
     
     
         116 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition does not have more than one surfactant. 
     
     
         117 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises an oil and a surfactant. 
     
     
         118 . The nanoparticle composition of  claim 117 , wherein the oil and surfactant are present in a ratio ranging from 0.5-2.0. 
     
     
         119 . The nanoparticle composition of  claim 117 , wherein the oil and surfactant are present in a ratio ranging from 0.5-1.5. 
     
     
         120 . The nanoparticle composition of  claim 117 , wherein the oil and surfactant are present in a ratio ranging from 0.5-1.0. 
     
     
         121 . The nanoparticle composition of  claim 117 , wherein the oil and surfactant are present in a ratio ranging from 1.0-2.0. 
     
     
         122 . The nanoparticle composition of  claim 117 , wherein the oil and surfactant are present in a ratio ranging from 1.5-2.0. 
     
     
         123 . The nanoparticle composition of  claim 117 , wherein the percent of oil in the nanoparticle composition ranges from 1%-30%. 
     
     
         124 . The nanoparticle composition of  claim 117 , wherein the percent of oil in the nanoparticle composition ranges from 1%-20%. 
     
     
         125 . The nanoparticle composition of  claim 117 , wherein the percent of oil in the nanoparticle composition ranges from 1%-10%. 
     
     
         126 . The nanoparticle composition of  claim 117 , wherein the percent of oil in the nanoparticle composition is approximately 8%. 
     
     
         127 . The nanoparticle composition of  claim 117 , wherein the percent of oil in the nanoparticle composition is approximately 5%. 
     
     
         128 . The nanoparticle composition of  claim 117 , wherein the percent of surfactant in the nanoparticle composition ranges from 1%-30%. 
     
     
         129 . The nanoparticle composition of  claim 117 , wherein the percent of surfactant in the nanoparticle composition ranges from 1%-20%. 
     
     
         130 . The nanoparticle composition of  claim 117 , wherein the percent of surfactant in the nanoparticle composition ranges from 1%-10%. 
     
     
         131 . The nanoparticle composition of  claim 117 , wherein the percent of surfactant in the nanoparticle composition is approximately 8%. 
     
     
         132 . The nanoparticle composition of  claim 117 , wherein the percent of surfactant in the nanoparticle composition is approximately 5%. 
     
     
         133 . The nanoparticle composition of  claim 117 , wherein the oil is selected from the group consisting of almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, chamomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macadamia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils, and combinations thereof. 
     
     
         134 . The nanoparticle composition of  claim 117 , wherein the oil is soybean oil. 
     
     
         135 . The nanoparticle composition of  claim 117 , wherein the oil is selected from the group consisting of butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, Labrafac WL 1349, and combinations thereof. 
     
     
         136 . The nanoparticle composition of  claim 117 , wherein the surfactant is a nonionic detergent. 
     
     
         137 . The nanoparticle composition of  claim 117 , wherein the surfactant is selected from the group consisting of phosphoglycerides; phosphatidylcholines; dipalmitoyl phosphatidylcholine (DPPC); dioleylphosphatidyl ethanolamine (DOPE); dioleyloxypropyltriethylammonium (DOTMA); dioleoylphosphatidylcholine; cholesterol; cholesterol ester; diacylglycerol; diacylglycerolsuccinate; diphosphatidyl glycerol (DPPG); hexanedecanol; fatty alcohols such as polyethylene glycol (PEG); polyoxyethylene-9-lauryl ether; a surface active fatty acid, such as palmitic acid or oleic acid; fatty acids; fatty acid monoglycerides; fatty acid diglycerides; fatty acid amides; sorbitan trioleate (Span 85) glycocholate; sorbitan monolaurate (Span 20); polysorbate 20 (Tween-20); polysorbate 60 (Tween-60); polysorbate 65 (Tween-65); polysorbate 80 (Tween-80); polysorbate 85 (Tween-85); polyoxyethylene monostearate; surfactin; a poloxomer; a sorbitan fatty acid ester such as sorbitan trioleate; lecithin; lysolecithin; phosphatidylserine; phosphatidylinositol; sphingomyelin; phosphatidylethanolamine (cephalin); cardiolipin; phosphatidic acid; cerebrosides; dicetylphosphate; dipalmitoylphosphatidylglycerol; stearylamine; dodecylamine; hexadecyl-amine; acetyl palmitate; glycerol ricinoleate; hexadecyl sterate; isopropyl myristate; tyloxapol; poly(ethylene glycol)5000-phosphatidylethanolamine; poly(ethylene glycol)400-monostearate; phospholipids; synthetic and/or natural detergents having high surfactant properties; deoxycholates; cyclodextrins; chaotropic salts; ion pairing agents; and combinations thereof. 
     
     
         138 . The nanoparticle composition of  claim 117 , wherein the surfactant is Tween 80. 
     
     
         139 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises oily particles which are dispersed within an aqueous dispersion medium. 
     
     
         140 . The nanoparticle composition of  claim 139 , wherein the aqueous dispersion medium is selected from the group consisting of water, saline solution, phosphate buffered saline, short chain alcohols, 5% dextrose, Ringer's solution, lactated Ringer's injection, lactated Ringer's plus 5% dextrose injection, acylated Ringer's injection, Normosol-M, Isolyte E, and combinations thereof. 
     
     
         141 . The nanoparticle composition of  claim 139 , wherein the aqueous dispersion medium is water. 
     
     
         142 . The nanoparticle composition of  claim 139 , wherein the oily particles comprise an oil selected from the group consisting of almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, chamomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macadamia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, or wheat germ oil. 
     
     
         143 . The nanoparticle composition of  claim 139 , wherein the oily particles comprise soybean oil. 
     
     
         144 . The nanoparticle composition of  claim 139 , wherein the oily particles comprise an oil selected from the group consisting of butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, Labrafac WL 1349, and combinations thereof. 
     
     
         145 . The nanoparticle composition of  claim 1 , wherein the nanoparticle composition comprises aqueous particles which are dispersed within an oily dispersion medium. 
     
     
         146 . The nanoparticle composition of  claim 145 , wherein the aqueous particles comprise an aqueous substance selected from the group consisting of water, saline solution, phosphate buffered saline, short chain alcohols, 5% dextrose, Ringer's solution, lactated Ringer's injection, lactated Ringer's plus 5% dextrose injection, acylated Ringer's injection, or Normosol-M, Isolyte E. 
     
     
         147 . The nanoparticle composition of  claim 145 , wherein the aqueous particles comprise water. 
     
     
         148 . The nanoparticle composition of  claim 145 , wherein the oily dispersion medium is selected from the group consisting of almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, chamomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macadamia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils, and combinations thereof. 
     
     
         149 . The nanoparticle composition of  claim 145 , wherein the oily dispersion medium is soybean oil. 
     
     
         150 . The nanoparticle composition of  claim 145 , wherein the oil is selected from the group consisting of butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, Labrafac WL 1349, and combinations thereof. 
     
     
         151 . A nanoparticle composition comprising a population of particles having diameters between approximately 10 and approximately 300 nanometers, wherein said nanoparticle composition comprises at least one amphiphilic entity, and wherein the amphiphilic entity comprises a hydrophilic component and a hydrophobic component. 
     
     
         152 . A nanoparticle composition comprising a population of particles having diameters between approximately 10 and approximately 300 nanometers, wherein the nanoparticle composition was generated by exposure to high shear force; wherein said nanoparticle composition comprises at least one amphiphilic entity, and wherein the amphiphilic entity comprises a hydrophilic component and a hydrophobic component; and wherein the nanoparticle composition comprises at least one biologically active agent. 
     
     
         153 . A nanoparticle composition comprising:
 a population of particles having diameters between approximately 10 and approximately 300 nanometers;   an amphiphilic entity comprising a pullulan component and a polycaprolactone component; and   at least one biologically active agent;   wherein the nanoparticle composition was generated by exposure to high shear force.   
     
     
         154 . A pharmaceutical composition comprising any one of the nanoparticle compositions of  claim 1  or  151 - 153 . 
     
     
         155 . The composition of  claim 154 , wherein the composition is selected from the group consisting of a cream, a lotion, a gel, an ointment, a spray, a powder, an emollient, and combinations thereof. 
     
     
         156 . The composition of  claim 154 , wherein the composition is a cream. 
     
     
         157 . A method of administering a biologically active agent transdermally to a subject, comprising steps of:
 (a) providing a composition comprising a biologically active agent; and   (b) administering the composition to the skin of the subject.   
     
     
         158 . The method of  claim 157 , wherein the composition is administered transdermally using an adhesive patch. 
     
     
         159 . The method of  claim 157 , wherein the composition is administered transdermally using a spatula. 
     
     
         160 . The method of  claim 157 , wherein the composition is administered transdermally using a swab. 
     
     
         161 . The method of  claim 157 , wherein the composition is administered transdermally using a syringe without a needle. 
     
     
         162 . The method of  claim 157 , wherein the composition is administered transdermally using a gloved finger. 
     
     
         163 . The method of  claim 157 , wherein the composition is administered transdermally using an unprotected finger. 
     
     
         164 . The method of  claim 157 , wherein the composition is administered transdermally using a device that permits application of the composition to a target site on the skin without applying the composition to non-target sites of the skin. 
     
     
         165 . The method of  claim 157 , wherein all of the botulinum toxin permeates the skin. 
     
     
         166 . The method of  claim 157 , wherein at least 99% of the biologically active agent permeates the skin. 
     
     
         167 . The method of  claim 157 , wherein at least 95% of the biologically active agent permeates the skin. 
     
     
         168 . The method of  claim 157 , wherein at least 90% of the biologically active agent permeates the skin. 
     
     
         169 . The method of  claim 157 , wherein at least 75% of the biologically active agent permeates the skin. 
     
     
         170 . The method of  claim 157 , wherein at least 50% of the biologically active agent permeates the skin. 
     
     
         171 . The method of  claim 157 , wherein at least 25% of the biologically active agent permeates the skin. 
     
     
         172 . The method of  claim 153 , wherein at least 10% of the biologically active agent permeates the skin. 
     
     
         173 . The method of  claim 157 , wherein at least 1% of the biologically active agent permeates the skin. 
     
     
         174 . The method of  claim 157 , wherein the composition is administered in order to treat wrinkles, facial lines, and/or neck lines. 
     
     
         175 . The method of  claim 174 , wherein the wrinkles, facial lines, and/or neck lines are selected from the group consisting of hyperkinetic facial lines, facial wrinkles, platysma bands, décolleté bands, and combinations thereof. 
     
     
         176 . The method of  claim 175 , wherein the facial wrinkles involve one or more of the forehead region, glabellar region, frontalis region, temporalis region, rhytids region, or periorbital region. 
     
     
         177 . The method of  claim 157 , wherein the composition is administered in order to improve the appearance of the subject's skin. 
     
     
         178 . A method of administering biologically active agent transdermally to a subject, comprising steps of:
 (a) providing:
 (i) a subject; and 
 (ii) a composition comprising the nanoparticle composition of any one of  claim 1  or  151 - 153 ; and 
   (b) administering the composition to the skin of the subject.   
     
     
         179 . A method of treating wrinkles, facial lines, and/or neck lines, comprising steps of:
 (a) providing:
 (i) a subject exhibiting symptoms of wrinkles, facial lines, and/or neck lines; and 
 (ii) a composition comprising the nanoparticle composition of any one of  claim 1  or  151 - 153 ; and 
   (b) administering the composition to the skin of the subject such that symptoms are reduced.   
     
     
         180 . A method of delaying the onset of wrinkles, facial lines, and/or neck lines, comprising steps of:
 (a) providing:
 (i) a subject not exhibiting symptoms of wrinkles, facial lines, and/or neck lines; and 
 (ii) a composition comprising the nanoparticle composition of any one of  claim 1  or  151 - 153 ; and 
   (b) administering the composition to the skin of the subject such that the onset of symptoms is delayed.   
     
     
         181 . A method of manufacturing a nanoparticle composition, comprising steps of:
 providing a premix comprising one or more amphiphilic entities; and   subjecting the premix to high shear force or high pressure homogenization for a period of time and under conditions which achieve a nanoparticle composition of any one of  claim 1  or  151 - 153 .   
     
     
         182 . The method of  claim 181 , wherein the premix comprises a biologically active agent. 
     
     
         183 . The method of  claim 181 , wherein the premix comprises an oil. 
     
     
         184 . The method of  claim 181 , wherein the premix comprises a surfactant. 
     
     
         185 . A method of manufacturing a nanoparticle composition, comprising steps of:
 (a) providing a premix comprising an amphiphilic entity comprising a pullulan component and a polycaprolactone component;   (b) forming a solution comprising the premix; and   (c) subjecting the premix to high shear force or high pressure homogenization for a period of time and under conditions which achieve a nanoparticle composition of any one of  claim 1  or  151 - 153 .   
     
     
         186 . A method of manufacturing a nanoparticle composition, comprising steps of:
 (a) providing a premix comprising:
 (i) an amphiphilic entity comprising a pullulan component and a polycaprolactone component; and 
 (ii) a biologically active agent; 
   (b) forming a solution comprising the premix; and   (c) subjecting the solution to high shear force or high pressure homogenization for a period of time and under conditions which achieve a nanoparticle composition of any one of  claim 1  or  151 - 153 ;   wherein the oil and surfactant are present at a ratio ranging between 0.5-2.0 (by weight); and wherein the high shear force is generated by microfluidization.